Major Depressive Disorder - Understanding The Link Between The Brain And The Heart
Status:
Unknown status
Trial end date:
2020-12-01
Target enrollment:
Participant gender:
Summary
There is strong evidence that patients with major depressive disorder (MDD) have an increased
risk of developing coronary heart disease (CHD). This elevated risk is independent of
standard risk factors such as smoking, obesity, high cholesterol, diabetes, and high blood
pressure. The relative risk of developing CHD is proportional to the severity of depression
(the more severe the depression, the more likely the development of CHD).
The sympathetic nervous system (the part of your nervous system that makes your heart beat
harder and faster) is responsible for our "flight and fight" response to a threatening
situation. It has been determined that increased sympathetic nervous system activation occurs
in approximately one in three untreated patients with MDD (with no underlying CHD). There is
growing evidence linking elevated sympathetic activity to early stages of kidney dysfunction
and an increased incidence of cardiovascular (heart and blood vessel) disease development
(eg, heart attacks). Sympathetic nervous system activation over a prolonged period of time
may also be associated with abnormal blood pressure regulation and the development of insulin
resistance (an important feature of type 2 diabetes).
It has been suggested that a certain gene, known as the serotonin transporter (5-HTT) gene,
may be involved. In particular, work from our group indicates that a particular type of this
gene, the short form (or "short" allele) may be important in linking MDD, sympathetic nervous
activation, and increased cardiac risk.
This study aims to examine the role of the 5-HTT gene on cardiovascular risk factors
associated with elevated sympathetic activity in patients with MDD. Additionally, the study
will examine the effect of serotonin re-uptake inhibitor (SSRI) therapy on these parameters.
A clearer understanding of these systems and processes will allow for identification of
patients with increased cardiac risk and development of risk reduction strategies. Such
information is clinically significant given the link between cardiovascular disease and MDD.
Hypothesis 1: That MDD patients carrying the s allele of the 5-HTT transporter have higher
sympathetic activity than homozygous ll patients.
Hypothesis 2: that MDD patients with elevated sympathetic activity display early signs of
left ventricular hypertrophy (LVH) and diastolic dysfunction.
Hypothesis 3: That MDD patients with high sympathetic activity have greater morning surges in
blood pressure than patients with normal sympathetic activity.
Hypothesis 4: That MDD patients with elevated sympathetic activity display early signs of
insulin resistance.
Hypothesis 5: That SSRI therapy, in particular in those who carry the s allele of the 5-HTT,
has a favourable effect on blood pressure variability and morning surge in blood pressure,
sympathetic stress reactivity, and markers of insulin resistance.
Phase:
Phase 4
Details
Lead Sponsor:
Baker Heart and Diabetes Institute Baker IDI Heart and Diabetes Institute
Collaborators:
Ballarat Health Services Monash Medical Centre The Alfred